全身麻醉药物对发育期大脑影响的争鸣

麻醉药物作用于N-甲基-D-天冬氨酸(NMDA)受体和(或)γ氨基丁酸(GABA)引起发育期动物大脑神经退行性变和成年后认知功能障碍,且神经元凋亡或功能受损具有年龄、接触时间和剂量的依赖性。然而麻醉药物诱导神经细胞凋亡的假说仍存在争议。麻醉药物引起的凋亡是病理性凋亡还是生理性凋亡及其与与神经认知功能障碍间的因果关系尚不清楚。动物实验中不同种属动物麻醉/镇痛所需要的药物剂量、发育易感期各不相同,因此动物实验结果不能直接应用于临床。临床上全麻药物对婴幼儿神经毒性的临床研究证据尚不充分,仍需进一步获取多中心、大样本人类研究数据,以证实麻醉药物与发育期大脑退行性变的因果关系,阐述其机制,指导临床医师的工作。本文综述了全身麻醉药物对发育期大脑影响的研究进展。     

Pregabalin in clinical psychiatry and addiction: pros and cons

Pregabalin acts as a presynaptic modulator of excitatory neurotransmitter release, binding to the α2-δ subunit protein of voltage-gated calcium channels. Pregabalin use is becoming widespread in the psychiatric scenario. Data are encouraging, with some good evidence for efficacy in anxious spectrum, benzodiazepine abuse/dependence, and alcoholism. The abuse potential, however, is an issue that should be taken into account, mostly in subjects at risk for developing substance/alcohol misuse.     

Nano anti-cancer drugs: pros and cons and future perspectives

For last one decade, scientists are working for developing nano anti-cancer drugs with claim of ideal ones due to their targeted chemotherapic nature. These drugs have many beneficial properties such as targeted drug delivery and gene therapy modalities with minimum side effects. This article describes pros and cons and future perspectives of nano anti-cancer drugs. Efforts have been made to address importance, special features, toxicities (general, blood identities, immune system and environmental) and future perspectives of nano anti-cancer drugs. It was concluded that nano anti-cancer drugs may be magic bullet drugs for cancer treatment leading to bright future of the whole world.     

Pesticide use in developing countries

Chemical pesticides have been a boon to equatorial, developing nations in their efforts to eradicate insect-borne, endemic diseases, to produce adequate food and to protect forests, plantations and fibre (wood, cotton, clothing, etc.). Controversy exists over the global dependence on such agents, given their excessive use/misuse, their volatility, long-distance transport and eventual environmental contamination in colder climates. Many developing countries are in transitional phases with migration of the agricultural workforce to urban centres in search of better-paying jobs, leaving fewer people responsible for raising traditional foods for themselves and for the new, industrialized workforce. Capable of growing two or three crops per year, these same countries are becoming ‘breadbaskets’ for the world, exporting nontraditional agricultural produce to regions having colder climates and shorter growing seasons, thereby earning much needed international trade credits. To attain these goals, there has been increased reliance on chemical pesticides. Many older, nonpatented, more toxic, environmentally persistent and inexpensive chemicals are used extensively in developing nations, creating serious acute health problems and local and global environmental contamination. There is growing public concern in these countries that no one is aware of the extent of pesticide residue contamination on local, fresh produce purchased daily or of potential, long-term, adverse health effects on consumers. Few developing nations have a clearly expressed ‘philosophy’ concerning pesticides. There is a lack of rigorous legislation and regulations to control pesticides as well as training programs for personnel to inspect and monitor use and to initiate training programs for pesticide consumers.     

激素替代疗法的利与弊

激素替代疗法（hormone replacement therapy,HRT）是对围绝经期和绝经后妇女通过补充性激素,调整绝经过渡期紊乱的月经周期,缓解或根除绝经前后出现的症状（如心悸、发热、面颊潮红、生殖道萎缩干燥等症状）,提高生活质量的一种治疗方法。HRT治疗从开始使用至今,其利弊之争就没有停止过,     

Cannabinoids and cancer: pros and cons of an antitumour strategy

In the last two decades, research has dramatically increased the knowledge of cannabinoids biology and pharmacology. In mammals, compounds with properties similar to active components of Cannabis sativa, the so called 'endocannabinoids', have been shown to modulate key cell-signalling pathways involved in cancer cell growth, invasion and metastasis. To date, cannabinoids have been licensed for clinical use as palliative treatment of chemotherapy, but increased evidences showed direct antiproliferative actions of cannabinoid agonists on several tumour cells in vitro and in animal models. In this article, we will review the principal molecular pathways modulated by cannabinoids on cancer and summarize pros and cons evidence on the possible future use of endocannabinoid-based drugs in cancer therapy.     

Boric acid as reference substance: pros,cons and standardization

Boric acid (BA) has been successfully used as reference substance in some standard test guidelines. Due to the fact that previously selected reference substances present a significant risk to human health and/or are banned for environmental reasons, BA is being discussed for broader adoption in OECD or ISO guidelines. To provide input on BA data and contribute to the discussion on its suitability as a reference substance, in the present study BA was tested with two standard soil organisms, Enchytraeus albidus and Folsomia candida, in terms of survival, reproduction and avoidance. Additionally, published data on other organisms was analysed to derive the most sensitive soil dwelling invertebrate (hazard concentration–HC5). Results showed that BA affected the tested organisms, being two times more toxic for collembolans (LC50 = 96; EC50 = 54 mg/kg) than for enchytraeids (LC50 = 325; EC50 = 104 mg/kg). No avoidance behaviour occurred despite the fact that BA affects earthworms. Actually, it is the recommended reference substance for the earthworm avoidance test. Clearly, the suitable performance of BA in one species should not be generalized to other species. Absolute toxicity is not an important criterion for the selection of a reference substance, but it has been proposed that effects should occur within a reasonable range, i.e. <1,000 mg/kg. We could confirm, compiling previous data that for most soil invertebrates, the EC50 is expected to be below 1,000 mg/kg. From these data it could be derived that the most sensitive soil dwelling invertebrate (HC5, 50%) is likely to be affected (EC10) at 28 (8–53) mg H₃BO₃/Kg, equivalent to 4.6 (1.4–8.7) mg boron/kg.     

The pros and cons of polyelectrolyte capsules in drug delivery

Polyelectrolyte multilayer microcapsules and nanocapsules are under review as multifunctional delivery systems. Tailoring functions in the entity of a single capsule is done by incorporation of functional polyelectrolytes or nanoparticles in between the layers during electrostatic self-assembly. The resulting capsules possess different properties such as controlled and triggered release, responsiveness to temperature, pH and light and could be navigated with a magnetic field. A variety of substances can be encapsulated and delivered to cells and tissues. Potential applications as well as in vivo experiments have recently been explored. Capsules made of biodegradable polymers showed low toxicity in vivo. Perspectives on and obstacles to a way of broader application are discussed.     

Controlled and continuous release ocular drug delivery systems: pros and cons

Topical ocular drug administration is the most preferred route for treating conditions affecting the surface of the eye as well as anterior segment diseases; this is mainly due to the rapid and localised drug action and patient acceptability. However, the ocular bioavailability is typically less than 5% from conventional ophthalmic dosage forms such as eye drops. This is mainly due to the unique anatomical and physiological features of the eye. One of the effective pharmaceutical approaches is to provide a controlled and continuous drug release to the surface of the eye to compensate drug loss by nasolacrimal drainage and non-productive absorption of the topically applied drug. This review provides a critical appraisal (advantages and drawbacks) of the different drug delivery strategies that provides controlled and continuous drug supply to the surface of the eye; it covers research conducted over the past three decades.     

Historical review of sample preparation for chromatographic bioanalysis: pros and cons

Sample preparation is a major task in a regulated bioanalytical laboratory. The sample preparation procedure significantly impacts assay throughput, data quality, analysis cost, and employee satisfaction. Therefore, selecting and optimizing an appropriate sample preparation method is essential for successful method development. Because of our recent expertise, this article is focused on sample preparation for high‐performance liquid chromatography with mass spectrometric detection. Liquid chromatography with mass spectrometric detection (LC‐MS) is the most common detection technique for small molecules used in regulated bioanalytical laboratories. The sample preparation technologies discussed are pre‐extraction and post‐extraction sample processing, protein precipitation (PPT), liquid–liquid extraction (LLE), offline solid‐phase extraction (SPE), and online solid‐phase extraction. Since all these techniques were in use for more than two decades, numerous applications and variations exist for each technique. We will not attempt to categorize each variation. Rather, the development history, a brief theoretical background, and selected references are presented. The strengths and the limitations of each method are discussed, including the throughput improvement potential. If available, illustrations from presentations at various meetings by our laboratory are used to clarify our opinion. Drug Dev Res 68:107–133, 2007. ©2007 Wiley‐Liss, Inc.     

The pros and cons of a single 'Euro-price' for drugs

Parallel trade in pharmaceuticals has become a major European Union policy issue with several 'solutions' being considered by the European Commission, Member State governments and the pharmaceutical industry in the 'Bangemann Process'. This paper discusses the issues from an economic and public policy perspective--considering the economic cases for differential pricing and for 'Euro-prices', concluding that the economic case for parallel trade--to achieve convergence of prices--is not applicable to pharmaceuticals. It argues that health economic evaluation is not an appropriate tool to set 'Euro-prices' because of differences in clinical practice and in resource use and cost across countries. Pricing rules should reflect local willingness to pay for innovation. It concludes, however, that in the absence of policy changes there is a strong likelihood of companies refusing to supply new innovative products at low prices to traditionally 'low price' countries in order to avoid parallel trade undermining prices obtained elsewhere in Europe, with significant implications for the welfare of patients in those countries.     

Delayed preconditioning via Angiotensin-converting enzyme inhibition: pros and cons from an experimental study

1. Bradykinin B(2) receptor activation confers preconditioning from ischaemic injury. In the present study, we tested whether an angiotensin-converting enzyme (ACE) inhibitor (captopril) could mediate delayed preconditioning and, thus, cardioprotection. 2. New Zealand white rabbits received 15 mL infusion of either saline (control group; n = 7) or drugs (0.3 mg/kg captopril (CAP group; n = 7) or 0.3 mg/kg captopril + 0.1 mg/kg HOE 140 (CAPHOE group; n = 7)) via a marginal ear vein over 30 min. After 24 h, hearts were connected to a Langendorff apparatus and buffer perfused. The experimental protocol consisted of 20 min global normothermic hypoxia, followed by 120 min reperfusion. 3. Compared with baseline, the mean (SEM) contractile state (= dP/dt(max)) at 120 min reperfusion was decreased to 42 +/- ;23, 72 +/- ;16 (*P < 0.05 vs control) and 49 +/- ;22% in the control, CAP and CAPHOE groups, respectively. Early relaxation (= dP/dt(min)) was reduced to 55 +/- ;28, 73 +/- ;15 (*P < 0.05 vs control) and 52 +/- ;19% in the control, CAP and CAPHOE groups, respectively. The estimate for myocardial oxygen consumption (MVO(2)= rate-pressure product) was decreased to 52 +/- ;15, 69 +/- ;24 (*P < 0.05 vs control) and 56 +/- ;15% in the control, CAP and CAPHOE groups, respectively. Similarly, coronary flow was decreased in the control, CAP and CAPHOE groups to 49 +/- ;20, 67 +/- ;18 and 46 +/- ;19%, respectively. In contrast, ventricular extrasystoles during reperfusion were significantly elevated in both the CAP and CAPHOE groups (1.3 +/- ;0.2 and 1.1 +/- ;0.3 /min, respectively) compared with control (0.4 +/- ;0.2 /min). 4. Captopril confers delayed preconditioning against stunning via a B(2) receptor-mediated pathway. This pharmacological preconditioning protects against systolic and diastolic stunning, against vascular stunning and preserves cardiac metabolism. In addition to its accepted cardioprotective effects in early preconditioning, captopril should induce delayed preconditioning (e.g. for routine interventional cardiology or in elective cardiac surgery).